p-phenylenediamine derivatives are key precursors for oxidative hair dyeing. They are usually used to generate dark shades. p-phenylenediamine derivatives have been used for decades for hair dyeing. Among the p-phenylenediamine derivatives, a particularly favourable candidate, namely 2-methoxymethyl-p-phenylenediamine has been identified. This dye precursor is particularly advantageous in that it is typically characterised by a lower sensitizing potential than traditional p-phenylenediamine or p-toluenediamine dye precursors.
In the past, the industry already published different synthetic routes to manufacture 2-methoxymethyl-p-phenylenediamine (I) or salts thereof.
For example, US2003/0041392A1 discloses a process for the preparation of 2-methoxymethyl-p-phenylenediamine (I) via a Smiles rearrangement in one of the intermediate steps.
Another possible synthetic route has been disclosed in WO2012044758A1. This synthetic route comprises a combination of steps starting with 2-chlorobenzylchloride and methanol to form the methoxymethyl intermediate. Nitration occurs in 4 position and activates the chloride as leaving group. Substitution of the chloride by an amino donor, preferably using benzylamine, requires a phase-transfer catalyst to obtain the aniline intermediate. Final hydrogenation leads to the desired 2-methoxymethyl-p-phenylenediamine. One of the disadvantages of this method is that the overall yield may be relatively low and in some cases an insufficiency regarding the carbon balance can be observed.
An alternative synthetic route for preparing p-phenylenediamine by self-coupling of aniline has been disclosed in EP0013643A1. However, one of the disadvantages of this synthetic route is that some by-products such as amino biphenyl may be produced. These compounds are critical due to their toxicological profile and therefore this limits the use of this synthesis route.

Finally, a diazotation synthetic route has been disclosed in Rajaganesh, Ramanathan et al; Organic Letters, 14(3), 748-751; 2012. However, this synthetic route is not satisfactory in term of purity results and some by-products such as amino biphenyl may also be produced.

Therefore, there still exists the need to provide a new process for preparing 2-methoxymethyl-2-phenylenediamine (I) a cosmetically acceptable salt thereof, or mixture thereof which is particularly cost effective. This process should also be able to provide materials with a low impurity level. Furthermore, the process should also reduce the risk of non-controllable side reactions.
The inventors have surprisingly found that at least some of these needs may be met by a process according to the present invention comprising an economical recycling of the literature known key intermediate 2-hydroxymethylaniline (II).